Patients suffering from manic, depressive, schizoaffective, and anxiety disorders are longitudinally evaluated and treated. Double-blind placebo-controlled trials are conducted and have demonstrated that the anticonvulsant carbamazepine is useful in treating both manic and depressive illness. This discovery envolved from the use of animal models such as kindling and cocaine sensitization whih provided clues to mechanisms underlying progressive development of behavioral pathology. Cocaine sensitization in animals is environmental context specific, related to conditioning variables, and modulated by neuropeptides and sex hormones. In patients with affective illness and normal volunteers, neurotransmitters and metabolites, hormones, and peptides implicated in the regulation of mood and behavior are measured in blood, urine, and cerebrospinal fluid as an approach to studying normal and pathological brain function. Alterations in cognitive function, neurophysiology, and biochemistry are explored in relation to clinical response to anticonvulsants, dopaminergic and noradrenergic receptor agonists, the paradoxical therapeutic effects of sleep deprivation in depression, and related psychobiological approaches to understanding and treating mood and anxiety disorders.